The proposed research is designed to follow up on the considerable amount of evidence that 1) indicated that parafollicular cells of the mammalian thyroid gland contains both calcitonin and serotonin and 2) supports the hypothesis that thyroidal serotonin may act as a follicular cell activator. We propose continuing our investigation of the ultrastructural cytophysiology of thyroid parafollicular cells and also of thyroidal aminergic mechanisms. Many of the proposed studies will be carried out in the bat because its thyroid gland has been found to contain large numbers of parafollicular cells with seasonal synchronization of function. Other studies will be carried out in the sheep because the sheep's thyroid is large and is therefore an ideal model for some of the biochemical studies. We also propose the continuation of eludidating intracellular secretory pathways of thyroid follicular cells and bone cells utilizing the bat as a model due to the synchronization of activity of these cells during the yearly life cycle. We intend to utilize enzyme cytochemical and autoradiographic techniques to define the possible role of extracellular vesicles and paracrystalloid inclusions in follicular cell function and the role of the osteocyte in bone resorption. Properties of thyroid aminergic mechanisms to be studied will include subcellular storage mechanisms for serotinin, tryptophan and serotonin uptake and its relation to thyroid activity, serotonin release and the role of serotonin in regulating follicular cell pseudopod formation. We also propose to continue our study of the role of the parafollicular cell during development employing an integrated approach in an attempt to determine if parafollicular cell secretion occurs prior to birth.